The endothelial cell of the lung is highly sensitive to radiation and there is evidence that it is one of the first, or the first, lung cell to show morphological damage after radiation. Alteration in the integrity of the endothelial cell is likely to result in increased vascular permeability and pulmonary interstitial and intra-alveolar pathology. Our plan is to characterize radiation damage to the cultured endothelial cell morphologically, biochemically, and functionally. 137Cs will be the source of radiation. Biochemical mechanisms by which radiation damage to this cell occurs will be studied and protective mechanisms against damage will be evaluated. In particular, several biochemical processes known to be factors in oxidant toxicity (formation of superoxide, hydrogen peroxide and hydroxyl radical) and enzymatic activities of the cell that provide protection against them (including superoxide dismutase, catalase, peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase) will be assessed after radiation. This will allow a comparison of the mechanisms of radiation and oxidant toxicities and protection against them. Compounds including bleomycin, disulfiram, WR2721, endotoxin, and diethyldithiocarbamate will be evaluated for their effects on endothelial cells and for their potentiation of or protection against radiation damage. Cells will be studied at high and low O2 tension after radiation to assess the effects of these parameters on toxicity. Cells wll be studied in the presence and absence of serum to determine possible influence of circulatory factors on radiation injury. Studies will be carried out on the possible interactions between endothelial cells and fibroblasts before and after radiation in a attempt to better understand the pathogenesis of radiation fibrosis. It is hoped that these assessments of pulmonary endothelial cells in an in vitro system will ultimately provide insight into means for protection against radiation injury to the lung in patients undergoing radiotherapy and that the information will give us a broader understanding of toxic injury to the lung in general.